A Phase Ib Study With Expansion Cohorts Evaluating the Safety and Efficacy of Mosunetuzumab in Combination With Platinum-Based Salvage Chemotherapy in Patients With Relapsed/Refractory Aggressive B Cell Lymphoma
This is a two-arm, open-label, phase Ib single-site study with expansion cohorts testing the addition of mosunetuzumab to intensive platinum-based salvage chemotherapy in patients with relapsed/refractory aggressive B cell lymphoma. The hypothesis of this study is that mosunetuzumab can be safely combined with platinum-based salvage chemotherapy in this patient population, and that this approach may outperform chemoimmunotherapy approaches that instead incorporate rituximab retreatment. The enrolling physician's choice of the chemotherapy backbone will determine a patient's assigned study arm (Arm A = DHAX, Arm B = ICE). The two arms will accrue patients to phase Ib independently.
• Diagnosis of large, high-grade, or transformed B cell lymphoma or follicular lymphoma grade 3B that is refractory to or has relapsed after anti-CD20 mAb plus anthracycline-containing combination chemotherapy. A biopsy immediately prior to enrollment is not mandatory.
• Must have received at least one prior line of systemic treatment containing conventional cytotoxic chemotherapy for lymphoma. Conventional cytotoxic chemotherapy with or without an anti-CD20 mAb for prior/underlying indolent NHL (with or without maintenance/extended-use anti-CD20 mAb) will count as one line of systemic therapy.
• At least 18 years of age.
• ECOG performance status ≤ 2
• Adequate hematologic function (unless due to underlying lymphoma per the investigator), defined as follows:
‣ Absolute neutrophil count ≥ 1,000/mcL
⁃ Platelets ≥ 75,000/mcL without platelet transfusion within 14 days prior to the first dose of mosunetuzumab
⁃ Hemoglobin ≥ 8 g/dL without red blood cell transfusion within 7 days prior to the first dose of mosunetuzumab
• Patients with extensive bone marrow involvement by lymphoma and/or disease-related cytopenias (e.g., immune thrombocytopenia) may be enrolled if the following criteria are met:
‣ Absolute neutrophil count ≥ 500/mcL
⁃ Platelet count ≥ 50,000/mcL without platelet transfusion within 14 days prior to the first dose of mosunetuzumab
⁃ No red blood cell transfusion within 7 days prior to the first dose of mosunetuzumab
• Normal laboratory values:
‣ Serum total bilirubin ≤ 1.5 x IULN (or ≤ 3 x IULN for patients with Gilbert's syndrome)
⁃ AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
⁃ Serum creatinine ≤ 1.5 x IULN or creatinine clearance ≥ 50 mL/min by Cockcroft-Gault
• The effects of mosunetuzumab on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (as defined in protocol) prior to study entry, for the duration of study treatment, and for 3 months following the final dose of mosunetuzumab. Specifically, women must remain abstinent or use contraceptive methods with a failure rate of \<1% per year during the treatment period and for 3 months after the final dose of mosunetuzumab as applicable. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol with a female partner of childbearing potential or pregnant female partner must also agree to use adequate contraception prior to the study, for the duration of study treatment, and for 3 months following the final dose of mosunetuzumab.
• Ability to understand and willingness to sign an IRB approved written informed consent document.